PDGF-C and -D are the major isoforms expressed in human retinal pigment epithelium (RPE). Functionally active PDGFR-&#945; and -&#946; are mainly expressed at the apical membrane. PDGF-BB, -CC, -DD significantly increased proliferation while PDGF-BB, -AB and -DD significantly increased cell migration, suggesting a critical role in RPE pathophysiology. A pro-inflammatory cytokine mixture (TNF&#945;/IL-1&#946;/IFN&#947;) abrogated PDGF-induced proliferation and migration by inducing apoptosis, and by disrupting the cytoskeleton and tight junctions. Further study demonstrated that IFN&#947; alone significantly inhibited human fetal RPE (hfRPE) proliferation, which was significantly blocked by JAK inhibitor I, while Type I IFN, IFN&#945; and IFN&#946; did not affect hfRPE proliferation under the same culture conditions. Addition of IFN&#947; to the basal, but not the apical bath significantly increased Jv across hfRPE monolayer. In contrast to hfRPE, the proinflammatory cytokine mixture, and IFN&#947; by itself, stimulated the proliferation of choroidal cells. These findings suggest a complex role of pro-inflammatory cytokines, particularly IFN&#947;, in overcoming local proliferative/wound healing responses of RPE at the retina/RPE/choroid interface.